Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects

Catherine J Spellicy; Joy Norris; Renee Bend; Caleb Bupp; Paul Mester; Tracy Reynolds; Jane Dean; Yunhui Peng; Emil Alexov; Charles E Schwartz; Roger S Stevenson; Michael J Friez

doi:10.1038/s41431-017-0025-y

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Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects

Journal article

Open access

Peer reviewed

Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects

Catherine J Spellicy, Joy Norris, Renee Bend, Caleb Bupp, Paul Mester, Tracy Reynolds, Jane Dean, Yunhui Peng, Emil Alexov, Charles E Schwartz, …

European journal of human genetics : EJHG, Vol.26(3), pp.420-427

03/01/2018

DOI: 10.1038/s41431-017-0025-y

PMCID: PMC5838979

PMID: 29358613

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https://doi.org/10.1038/s41431-017-0025-yView

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Abstract

Neural tube defects (NTDs) remain one of the most serious birth defects, and although genes in several pathways have been implicated as risk factors for neural tube defects via knockout mouse models, very few molecular causes in humans have been identified. Whole exome sequencing identified deleterious variants in key apoptotic genes in two families with recurrent neural tube defects. Functional studies in fibroblasts indicate that these variants are loss-of-function, as apoptosis is significantly reduced. This is the first report of variants in apoptotic genes contributing to neural tube defect risk in humans.

Apoptosis

Drug Resistance

Pregnancy

Adult

Apoptotic Protease-Activating Factor 1 - genetics

Apoptotic Protease-Activating Factor 1 - metabolism

Caspase 9 - genetics

Caspase 9 - metabolism

Cells, Cultured

Female

Fetal Death

Fibroblasts - metabolism

Fibroblasts - pathology

Folic Acid - administration & dosage

Folic Acid - therapeutic use

Humans

Loss of Function Mutation

Male

Neural Tube Defects - drug therapy

Neural Tube Defects - genetics

Neural Tube Defects - pathology

Details

Title: Subtitle: Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects
Creators: Catherine J Spellicy - Greenwood Genetic Center
Joy Norris - Greenwood Genetic Center
Renee Bend - Greenwood Genetic Center
Caleb Bupp - Spectrum Health
Paul Mester - Greenwood Genetic Center
Tracy Reynolds - Greenwood Genetic Center
Jane Dean - Greenwood Genetic Center
Yunhui Peng - Clemson University
Emil Alexov - Clemson University
Charles E Schwartz - Greenwood Genetic Center
Roger S Stevenson - Greenwood Genetic Center
Michael J Friez - Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC, 29649, USA. friez@ggc.org
Resource Type: Journal article
Publication Details: European journal of human genetics : EJHG, Vol.26(3), pp.420-427
DOI: 10.1038/s41431-017-0025-y
PMID: 29358613
PMCID: PMC5838979
ISSN: 1018-4813
eISSN: 1476-5438
Grant note: R01 GM093937 / NIGMS NIH HHS
Language: English
Date published: 03/01/2018
Academic Unit: Internal Medicine
Record Identifier: 9984691514202771

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